ArticleBMC medicine2022
Identification of a window of androgen sensitivity for somatic cell function in human fetal testis cultured ex vivo.
Article in BMC medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
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Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- Genetic and genomic insights into male reproductive tract development.Fertility and sterility · 2025Pooled it
- Single-cell resolution uncovers neighboring cell subtypes that share steroidogenic capacity during fetal testis development.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Anoscrotal distance and urogenital anomalies in ART-conceived male infants: a retrospective cohort study.Frontiers in reproductive health · 2025Article
- Associations between maternal periconceptional exposure to PMScientific reports · 2024Article
- Hormone Regulation in Testicular Development and Function.International journal of molecular sciences · 2024Review
- Fetal Leydig cells: What we know and what we don't.Molecular reproduction and development · 2024Review
- The epidemiology of cryptorchidism and potential risk factors, including endocrine disrupting chemicals.Frontiers in endocrinology · 2024Review
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Authors and funding
17 authors at 7 institutions in 2 countries.
Funding
Abstract
backgroundReduced androgen action during early fetal development has been suggested as the origin of reproductive disorders comprised within the testicular dysgenesis syndrome (TDS). This hypothesis has been supported by studies in rats demonstrating that normal male development and adult reproductive function depend on sufficient androgen exposure during a sensitive fetal period, called the masculinization programming window (MPW). The main aim of this study was therefore to examine the effects of manipulating androgen production during different timepoints during early human fetal testis development to identify the existence and timing of a possible window of androgen sensitivity resembling the MPW in rats.
methodsThe effects of experimentally reduced androgen exposure during different periods of human fetal testis development and function were examined using an established and validated human ex vivo tissue culture model. The androgen production was reduced by treatment with ketoconazole and validated by treatment with flutamide which blocks the androgen receptor. Testicular hormone production ex vivo was measured by liquid chromatography-tandem mass spectrometry or ELISA assays, and selected protein markers were assessed by immunohistochemistry.
resultsKetoconazole reduced androgen production in testes from gestational weeks (GW) 7-21, which were subsequently divided into four age groups: GW 7-10, 10-12, 12-16 and 16-21. Additionally, reduced secretion of testicular hormones INSL3, AMH and Inhibin B was observed, but only in the age groups GW 7-10 and 10-12, while a decrease in the total density of germ cells and OCT4
conclusionsThis study showed that reduced androgen action during early development affects the function and density of several cell types in the human fetal testis, with similar effects observed after ketoconazole and flutamide treatment. The effects were only observed within the GW 7-14 period-thereby indicating the presence of a window of androgen sensitivity in the human fetal testis.
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